Origin of Proteins

Well thank you! :slight_smile:
I’ve seen lots of good arguments to falsify it, and more that it doesn’t mean what Gpuccio thinks it means, but not necessarily in this thread (most of which I still haven’t read).

Simplifying works both ways: If deep time is a requirement, that needs to be stated and justified. I honestly this that’s more of a complication than a simplification.

The problems here, IMO, ultimately goes back to Gpuccio. That there is so much room for argument about his methods seems to indicate that he did not state his methods clearly enough. Some of the arguments suggest he does not understand his own methods. :-/

Since, according to you, Bsc4 evolved recently, there is no way to calculate its FI. But 400 millions years latter, it would then become possible. This how gpuccio’s method works. And it makes perfect sense.

I want to see the equations and methods you are using when you say that proteins evolving in the lab have low FI.

No, it doesn’t make perfect sense. Break it down! :slight_smile:

Why does the same calculation on something old versus something new have different meaning?

I would love to know which are those arguments you think have falsified gpuccio.

I’am tired now. I hope I can answer you tomorrow.

When did I make this claim?

I actually agree, but I would make the same claim for a 400 million year old protein. All we get is an artifact of the diversity of the clade in which it happened to originate, the strength of purifying selection operating on it over this period of time, and the rate of molecular evolution in the lineages that make up that clade.
As such, we never really get an actual estimate of it’s FI, because we will never be able to determine whether there are strictly more functional sequences out there that are selected against because they have lower fitness, and the clade in which it evolved has limited diversity.

That’s been my whole damn criticism from the beginning. I am glad you’re starting to see, even if only for this limited example, why this FI nonsense is useless.

But 400 millions years latter, it would then become possible.

Why? Why 400 million years? How do you tell the difference between the number of different sequences that are possible, and the number of sequnces that evolved but were constrained by purifying selection? How do you know variants you’re not seeing aren’t actually functional, but just have lower fitness and hence why they don’t appear in the population(because they were selected against)?

How do you know that there isn’t a similarly functional sequence much much further away in sequence space?

This how gpuccio’s method works. And it makes perfect sense.

No, it doesn’t. Because you’d STILL not be anywhere near having sampled the possible diversity out there. You seem to be saying something oddly fantastic, that 400 million years of evolution has the capacity to thoroughly sample close to all of sequence space for a long sequence. How do you figure that?

But isn’t your claim, essentially, that sequence space is so vast evolution never could sample even a tiny fraction of it for large sequences? You’re trying to have your cake and eat it too.

The standard of falsification could use a little improvement :slight_smile:

Just to be clear, measuring changes in living populations in the lab is not a valid way of testing the claim that evolution can’t produce proteins with 500+ bits of FI. Is this correct?

You’ve just made one yourself. What we are seeing is a contraint given to us by time, and clade diversity. And sequence space is so much more unfathomably vast, particularly for a long protein sequence, than all of evolutionary history have had the capacity to sample.

And yet you want to claim this almost infinitesimal sampling done is enough for us to conclude there’s probably very little more functional diversity out there.

It depends on the conditions in the lab. If you were to simulate a program like Weasel and keep the mutation rate low enough you could generate 500 bits of FI but you need the original FI in the experiment to do this.

If you are looking at a protein with a 600 million year evolutionary history, how do you factor in the “original FI”?

Good question. Will think about it. I am out for the rest of the day.

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The thief and 100 safes example was just plain wrong. Gpuccio wasn’t doing the math right, nor does it accurately represent how proteins and function actually work. Much was written about it; here, here, here.
How the math should be done is here.

No worries. I didn’t get home home from the airport last night until 2 AM, and was up before 7 AM. Not sure how I am still able to function. :crazy_face:

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What is the answer, Bill?

Please explain WHY it makes perfect sense a calculation with no time variable would return a completely different value depending on when the calculation was done instead of just asserting it. Bill sure can’t.

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The number of trials required required divided by the mutations per unit time you are measuring.

Example: 10 trials required one mutation per year takes 10 years. 10 trials two mutations per year takes 5 years.

What constitutes a “trial”? You keep forgetting to say.

That answer is so wrong it’s not even wrong.

Here is the answer:

10^12 new cells. 0.003 mutations per cell.

0.003 x 10^12 = 3 x 10^9 new mutations in a single generation.

Questions?